Date: 2013-07-05
Type of information: Initiation of preclinical development
phase: 2
Announcement: results
Company: Mologen (Germany)
Product: MGN1703 (lefitolimod)
Action
mechanism: immunotherapy product/TLR9 agonist. Lefitolimod (MGN1703) is based on dSLIM® (“double Stem Loop Immunomodulator”), a DNA-based TLR9 agonist developed by Mologen. dSLIM® activates the immune system against tumor-associated antigens by targeting various receptors on certain immune cells, primarily TLR9. Tumor-associated antigens (TAA) are released by cancer cells as a result of chemotherapy and radiation therapy. Once activated by dSLIM®, the immune system is able to overcome its fatal tolerance toward cancer cells and TAA and attacks them selectively. Treatment with lefitolimod (MGN1703) triggers a broad and strong activation of the immune system. Due to this mechanism of action, lefitolimod (MGN1703) has the potential to be applied to various indications.
Due to this universal mechanism of action, MGN1703 can be applied to different indications of cancer. An application is currently being submitted for an additional phase 2 clinical study with MGN1703, this time for the treatment of advanced lung cancer (NSCLC). The study should begin immediately after approval.
Disease: advanced colorectal cancer
Therapeutic area: Cancer - Oncology
Country:
Trial
details: The IMPACT study is a phase 2, randomized, placebo-controlled, double-blind, multicenter clinical study aiming to determine the efficacy of MGN1703 as maintenance therapy following first-line chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer. The first-line therapy is a typical combination of chemotherapy and bevacizumab, which is typically associated with significant adverse effects. During the study, patients were treated twice per week with MGN1703. In the control arm patients received a placebo. The treatment was continued until tumor progression was radiologically confirmed.
The primary endpoint of the study is to determine progression-free survival of the patient. Secondary study endpoints include determining the overall survival, progression-free and overall survival rates, as well as collecting immunological and pharmacodynamic data.
Latest
news: * On July 5, 2013, Mologen has announced that Prof. Dr. Hans-Joachim Schmoll has given an oral presentation at ESMO World Congress on Gastroinstestinal Cancer on the final analysis of the IMPACT trial with MGN1703. The abstract “Updated results of the phase 2 IMPACT trial: Maintenance with MGN1703 vs placebo in patients with advanced colorectal carcincoma (mCRC)” had been chosen by ESMO to be among the most noteworthy ones this year. Prof. Schmoll, study coordinator and Director of the Oncological and Hematological Department at Martin-Luther-Universitaet Halle-Wittenberg, presented the results on the primary and secondary endpoints median progression-free survival (PFS) and overall survival (OS). In addition he reported on long-term responders which had been observed in the trial. These data showed that patients selected according to a certain biomarker, namely Natural Killer T-cells (NKT-cells), might benefit even more from treatment with MGN1703. The analysis on patients with a proportion of activated NKT-cells above a threshold resulted in a PFS hazard ratio of 0.27 with a p-value of 0.007 in favor of MGN1703. As reported at the ASCO Annual Meeting 2013, other analyses showed that CEA normalization and radiological response after induction chemotherapy may similarly help identify patients with greater benefit when treated with MGN1703. In summary the now completed final analysis of the IMPACT study has strengthened the proof-of-concept for MGN1703 in terms of efficacy and safety due to the considerably longer follow up. Based on this, Mologen is currently preparing a pivotal international trial to confirm these results in a larger number of patients. In parallel, Mologen pushes forwards its licensing activities for this drug candidate.
* On May 14, 2012, Mologen has announced it has conducted an initial assessment of the phase 2 colorectal cancer study with MGN1703. The assessment of 55 patients showed that the primary endpoint, the prolongation of the median progression-free survival, was achieved. Progression-free survival describes the period in which a cancer disease does not get worse.
Median progression-free survival in the pre-defined target population (46 patients) was even more than doubled compared to the placebo control group with high statistical significance (p<0.02). The comparison of both groups also shows a statistically significant hazard ratio: The risk of tumor progression was less than half for patients treated with MGN1703 compared to the placebo group.
Also the progression-free survival rate after six months, which is one of the secondary endpoints, shows a clear and statistically significant difference between both patient groups.
In addition, the study re-confirmed the excellent safety profile for MGN1703. Treatment was well tolerated also over longer periods. For the most part minor to moderate side-effects such as minor episodes of fever, fatigue and reddening of the injection site occurred.
From diligent observation of the study development and following consultations with their scientific advisors, management decided to terminate patient recruitment prematurely. A total of 58 patients were enrolled in the study. Treatment of patients who are still in the study will be continued according to the protocol. Data on overall survival of all patients will continue to be collected.
Mologen will consult with the FDA and EMA on the basis of these data to agree on additional steps required for approval. Parallel to this, talks with potential partners regarding out-licensing of MGN1703 will be continued.
